This five year Center renewal builds on the neurobiology THEME of our previous nine years by examining the pathophysiology and treatment of cocaine and AIDS neurotoxicity. The Center projects range from preclinical neurobiology to human laboratory and clinical trials relevant to opioids and cocaine dependence, as well as HIV infection. During the last 5 years we have over 50 publications, 10 independent new grants, and substantial progress on all 7 projects. We now developed six new Major Projects for this Center renewal of which four are extensions of previous projects: 1. The HPA Axis and Neurobehavioral Effects of Cocaine, 2. Glucocorticoid Function in Cocaine Dependence, 3. SPECT and Microdialysis Measurements of Cocaine Abuse, 4,Lamotrigine for Cocaine Abuse in HIV+Patients. Two new projects have evolved from our pilot work and collaborations with both the General Medical Clinical Research Center and the AIDS Clinical Trials Unit at Yale: 5. Amiloride for Cocaine Associated Cerebral Perfusion Deficits, 6. Opiate Dependence Pharmacotherapy Effects on AIDS Antiviral medications. The CORE will continue to support collaborations with these other research Centers at Yale, to integrate across the Center's Major Projects and investigators, and to conduct 2-3 pilot studies per year with a focus on AIDS related treatments and neurobiology. These pilots include cortisol levels in early AIDS patients on methadone treatment and neuroimaging in AIDS patients with cognitive impairment.